The major area of study of this laboratory is the role of the epidermis as an immunological organ. We have found that epidermal Langerhans cells are derived from precursor cells in the bone marrow and play an essential role in many of the immunological reactions affecting the skin. We have also identified an epidermal Interleukin 1-like cytokine which may serve as a second signal in the generation of T cell responses as well as a proinflammatory agent affecting other cells - especially neutrophils. We have demonstrated that when murine epidermal Langerhans cells are cultured for 2-3 days they become very potent antigen presenting cells for allogeneic and autologous T cells compared to freshly prepared Langerhans cells. We have therefore utilized cultured Langerhans cells for the generation of primary immune responses in resting unsensitized T cells. We have demonstrated that when cultured cells are modified with hapten, they can generate primary immune responses. The sensitized T cells thus generated respond preferentially to the same hapten in vitro. We have, therefore, attempted to utilize this system for the generation of primary in vitro responses to tumor-associated antigens such as the Friend Leukemia Virus associated gp-70. We are also currently assessing the feasibility of performing these studies in cells derived from human beings. Recent studies demonstrate that cultured human Langerhans cells have enhanced antigen presenting capacity. The other major focus of this laboratory has been the study of the function of class II MHC bearing keratinocytes which appear in humans and mice during cell-mediated reactions in the skin. We have demonstrated that these cells can 1) present peptide fragments to T cell hybridomas, 2) serve as targets for class II specific cytotoxic T lymphocytes, and 3) induce secondary alloreactive T cell responses, although the first and third are performed only poorly. Recent studies demonstrate that these class II bearing keratinocytes induce specific immunological unresponsiveness in cloned T cells and in vivo in contact sensitization.